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Results for “evolution of cell shape”

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PubMed2003

Biological and ultrastructural effects of the anti-microtubule agent taxol against Trypanosoma cruzi.

Microtubules play fundamental roles in eukaryotic cells and have been investigated as target for drugs. Several studies showed the potential use of anti-microtubule agents against pathogenic protozoa. Taxol has been intensively studied in Leishmania spp. and microtubules have been considered as a promising antileishmanial drug target. It has been also shown that taxol interferes with the proliferation of Trypanosoma cruzi, leading to morphological alterations and interruption of nuclear division and cytokinesis. In the present work we show that T. cruzi bloodstream trypomastigotes were much more susceptible than epimastigotes, and in both forms taxol caused severe ultrastructural damage, especially associated to changes in the shape of the parasites. In trypomastigotes, different degrees of body contortion along the longitudinal axis and a marked dilatation of the flagellar pocket were detected. Treated epimastigotes presented a decrease in the electron density of the mitochondrial matrix, absence of mitochondrial cristae and an increase in the number of lipid droplets. Bizarre multi-flagellar epimastigotes were also detected, suggesting an interruption of the cytokinesis. Taxol caused no noticeable ultrastructural alterations on sub-pellicular and flagellar microtubules of both evolutive forms of T. cruzi. As already described in the literature, such structures in trypanosomatids are very resistant to microtubule disrupters when compared to those in mammalian cells. Taxol prevented the endocytosis of albumin-gold complexes by epimastigotes, and this result could be associated to the loss of the dynamic stability of the microtubules of the cytostome.

Animals↗
PubMed2006

Early frontotemporal dementia targets neurons unique to apes and humans.

OBJECTIVE: Frontotemporal dementia (FTD) is a neurodegenerative disease that erodes uniquely human aspects of social behavior and emotion. The illness features a characteristic pattern of early injury to anterior cingulate and frontoinsular cortex. These regions, though often considered ancient in phylogeny, are the exclusive homes to the von Economo neuron (VEN), a large bipolar projection neuron found only in great apes and humans. Despite progress toward understanding the genetic and molecular bases of FTD, no class of selectively vulnerable neurons has been identified. METHODS: Using unbiased stereology, we quantified anterior cingulate VENs and neighboring Layer 5 neurons in FTD (n = 7), Alzheimer's disease (n = 5), and age-matched nonneurological control subjects (n = 7). Neuronal morphology and immunohistochemical staining patterns provided further information about VEN susceptibility. RESULTS: FTD was associated with early, severe, and selective VEN losses, including a 74% reduction in VENs per section compared with control subjects. VEN dropout was not attributable to general neuronal loss and was seen across FTD pathological subtypes. Surviving VENs were often dysmorphic, with pathological tau protein accumulation in Pick's disease. In contrast, patients with Alzheimer's disease showed normal VEN counts and morphology despite extensive local neurofibrillary pathology. INTERPRETATION: VEN loss links FTD to its signature regional pattern. The findings suggest a new framework for understanding how evolution may have rendered the human brain vulnerable to specific forms of degenerative illness.

Aged↗
PubMed2003

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins.

The hardest part of replicating a genome is the beginning. The first step of DNA replication (called "initiation") mobilizes a large number of specialized proteins ("initiators") that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ring-shaped helicase onto the DNA double helix.

Animals↗
PubMed2001

Experimental study of precipitating systems; computerised analysis of the optical transmittance and associated noise.

The change of the transmittance in a precipitant system has been measured by using a focused laser beam into a precipitation cell in which the precipitate was generated by an injection technique. We have monitored the evolution of the transmittance on several precipitation processes with different chemicals (PbI2, PbSO4, BaSO4 and BaC2O4) and quantities of precipitated mass (20.0, 17.5, 15.0, 12.5 and 10.0 mg). The noise associated to the transmittance signal has been obtained by a numerical procedure based on computer analysis, finding that it provides information about particle shape features and nucleation kinetics.

Journal Article↗
PubMed1997

Regulation of cell differentiation by the Drosophila Jun kinase cascade.

Recent studies have defined a new Drosophila Jun amino-terminal kinase (DJNK) pathway. The first role that has been uncovered for this pathway is the control of cell differentiation and morphogenesis during the process of dorsal closure. This phosphorylation cascade has been conserved during evolution and several reports suggest that it becomes activated in response to the action of small GTPases. DJNK signalling impinges on transcription factors as DJun and Anterior open and eventually controls the expression of target genes such as decapentaplegic and puckered. Important progress has been made in the study of the coordination of DJNK and Decapentaplegic signalling during dorsal closure and their role in the control of cell shape changes--and possibly cell polarity--by promoting cytoskeletal changes.

Animals↗
PubMed1992

The evolutionary selection of DNA base pairs in gene-regulatory binding sites.

The DNA base-pair sequences that serve as gene-regulatory sites have been selected during evolution to provide an appropriate functional binding for a particular protein. In most cases, the function depends on the binding probability, which can be influenced both by the binding strength and by the abundance of the protein in the cell. As a consequence, the same function can be achieved with strong binding sites and a small amount of protein as with weak binding sites and a large amount of protein. However, increasing the protein burden will decrease the growth rate of the cells, even when all functions remain the same. Thus, for maximal growth, the protein levels should be as low as possible and the binding correspondingly strong. On the other hand, sequences with a weaker binding can be formed in many more ways and are, therefore, more probable, and random mutations are more likely to produce them. Thus, the selection pressure against an increased protein burden can be balanced against the random mutational drift in the recognition sequences, thereby tying together the statistics of base-pair choice, the binding strength, and the protein burden. In terms of this model, the selection pressure can be estimated from the properties of a gene-regulatory protein and its recognition sites. A key feature is the mutational randomization pressure that appears as a fundamental force shaping the optimal solutions that provide maximal growth. The model is tested on a number of gene-regulatory systems in Escherichia coli. The same principles should hold for all proteins for which overall activity in the cell is proportional to abundance; then the selective pressure to increase the efficiency of an individual protein cannot be larger than the selective pressure to decrease the total protein burden.

Base Composition↗
PubMed2000

Symbiosis and pathogenesis: evolution of the microbe-host interaction.

Symbiotic and pathogenic bacteria have in common that they live in or on host organisms or host cells. To make a successful living in eukaryotic hosts, bacteria must possess the traits to recognize a given host and establish adherence. When the bacterial location is internal or intracellular, they must further have the ability to invade, to establish a niche, and finally to multiply within a host. The underlying mechanisms which allow this form of existence show similarities between symbiotic and pathogenic bacteria. The final outcome, however, may result in a wide spectrum of consequences for the host ranging from the acquisition of novel metabolic pathways to damage or death. Despite the vastly different forms of interactions, symbiotic and pathogenic bacteria have in common that they are adapted to a particular environmental niche represented by the host organism or compartment thereof. This contribution reviews the evolutionary forces which have shaped the microbial-host interactions. Particular emphasis is placed on the genetic and molecular mechanisms that drive bacterial evolution in response to the selective pressures of the host environment.

Animals↗
PubMed1977

[Electron microscopy features of renal changes in chronic lead poisoning (author's transl)].

The Authors report the results of a renal morphological study carried out on eight patients with chronic lead poisoning. The ultrastructural analysis showed changes, mainly involving the proximal tubules, as follows: 1) degenerative pattern (swollen mitochondria, dilated endoplasmic reticulum and scanty microvilli); 2) signs of metabolic hyperactivity (intranuclear granular inclusions, odd shaped nuclei); 3) regenerative pattern (poorly differentiated cells with few microvilli, shallow infoldings of basal cell membranes). In the glomeruli the most characteristic finding was a mesangial reaction. The basement membrane, in some cases, appeared to be thickened and the visceral epithelial cells hypertrophic. Interstitial fibrosis was present, as well as, occasionally, a certain degree of arteriolar hyperplasia. These data appear to confirm that chronic lead nephropathy has an extremely slow evolution.

Adult↗
PubMed2006

Cell biology of mitochondrial dynamics.

Mitochondria are the product of an ancient endosymbiotic event between an alpha-proteobacterium and an archael host. An early barrier to overcome in this relationship was the control of the bacterium's proliferation within the host. Undoubtedly, the bacterium (or protomitochondrion) would have used its own cell division apparatus to divide at first and, today a remnant of this system remains in some "ancient" and diverse eukaryotes such as algae and amoebae, the most conserved and widespread of all bacterial division proteins, FtsZ. In many of the eukaryotes that still use FtsZ to constrict the mitochondria from the inside, the mitochondria still resemble bacteria in shape and size. Eukaryotes, however, have a mitochondrial morphology that is often highly fluid, and in their tubular networks of mitochondria, division is clearly complemented by mitochondrial fusion. FtsZ is no longer used by these complex eukaryotes, and may have been replaced by other proteins better suited to sustaining complex mitochondrial networks. Although proteins that divide mitochondria from the inside are just beginning to be characterized in higher eukaryotes, many division proteins are known to act on the outside of the organelle. The most widespread of these are the dynamin-like proteins, which appear to have been recruited very early in the evolution of mitochondria. The essential nature of mitochondria dictates that their loss is intolerable to human cells, and that mutations disrupting mitochondrial division are more likely to be fatal than result in disease. To date, only one disease (Charcot-Marie-Tooth disease 2A) has been mapped to a gene that is required for mitochondrial division, whereas two other diseases can be attributed to mutations in mitochondrial fusion genes. Apart from playing a role in regulating the morphology, which might be important for efficient ATP production, research has indicated that the mitochondrial division and fusion proteins can also be important during apoptosis; mitochondrial fragmentation is an early triggering (and under many stimuli, essential) step in the pathway to cell suicide.

Animals↗
PubMed2000

[Molecular cell biology on morphogenesis of the fovea and evolution of the central vision].

Since Charles Darwin wrote "On the Origin of Species by Means of Natural Selection", it had been assumed that various eye types, from the compound eye to the camera eye, had originated independently in at least 40-60 different phyletic lines. However, the finding of Pax 6, the master control gene for eye morphogenesis, and the fact that its sequence is highly conserved throughout the animal kingdom indicated that the prototype eye in a primitive animal originated only once in evolution, and various eye types arose from the same origin. We recently found a Pax 6 mutation in a pedigree with foveal hypoplasia. Thus, the Pax 6 that appeared in light sensory cells of a primitive animal in ancient times may play a role in morphogenesis of the fovea, the most highly developed visual receptor. The fovea first appeared in evolution in the temporal retina of fishes. Then, in birds, the nasal fovea and bifoveal system with nasal and temporal foveas developed. The fovea disappeared in primitive mammals, and reappeared in primates. A residue of the fovea is conserved in the visual streak, and the disappearance and reappearance of the fovea, in primitive mammals and primates respectively, correlates with degeneration and restoration of cone pigment genes in photoreceptors. Humans inherited the temporal fovea that had first originated in fish eyes. Pax 6 is expressed in the entire eyeball at an early stage of development, and is also expressed widely in the retina to determine its differentiation. To determine the position of the fovea, retinal cells are abundant in the visual streak, probably because expression of Pax 6 is regulated by patterning of the dorsoventral axis of the eyeball. Signaling molecules, discharged from the front of the face, also regulate Pax 6 expression, and determine position of the fovea, visual axis, angle gamma, growth of the eyeball, and shape of the visual field. Further investigation of nerve pathfinding system from the fovea to the central nervous system will clarify the origin of the central vision, and contribute to human welfare.

Animals↗
PubMed2003

'Antifreeze' glycoproteins from polar fish.

Antifreeze glycoproteins (AFGPs) constitute the major fraction of protein in the blood serum of Antarctic notothenioids and Arctic cod. Each AFGP consists of a varying number of repeating units of (Ala-Ala-Thr)n, with minor sequence variations, and the disaccharide beta-D-galactosyl-(1-->3)-alpha-N-acetyl-D-galactosamine joined as a glycoside to the hydroxyl oxygen of the Thr residues. These compounds allow the fish to survive in subzero ice-laden polar oceans by kinetically depressing the temperature at which ice grows in a noncolligative manner. In contrast to the more widely studied antifreeze proteins, little is known about the mechanism of ice growth inhibition by AFGPs, and there is no definitive model that explains their properties. This review summarizes the structural and physical properties of AFGPs and advances in the last decade that now provide opportunities for further research in this field. High field NMR spectroscopy and molecular dynamics studies have shown that AFGPs are largely unstructured in aqueous solution. While standard carbohydrate degradation studies confirm the requirement of some of the sugar hydroxyls for antifreeze activity, the importance of following structural elements has not been established: (a) the number of hydroxyls required, (b) the stereochemistry of the sugar hydroxyls (i.e. the requirement of galactose as the sugar), (c) the acetamido group on the first galactose sugar, (d) the stereochemistry of the beta-glycosidic linkage between the two sugars and the alpha-glycosidic linkage to Thr, (e) the requirement of a disaccharide for activity, and (f) the Ala and Thr residues in the polypeptide backbone. The recent successful synthesis of small AFGPs using solution methods and solid-phase chemistry provides the opportunity to perform key structure-activity studies that would clarify the important residues and functional groups required for activity. Genetic studies have shown that the AFGPs present in the two geographically and phylogenetically distinct Antarctic notothenioids and Arctic cod have evolved independently, in a rare example of convergent molecular evolution. The AFGPs exhibit concentration dependent thermal hysteresis with maximum hysteresis (1.2 degrees C at 40 mg x mL-1) observed with the higher molecular mass glycoproteins. The ability to modify the rate and shape of crystal growth and protect cellular membranes during lipid-phase transitions have resulted in identification of a number of potential applications of AFGPs as food additives, and in the cryopreservation and hypothermal storage of cells and tissues.

Animals↗
PubMed2002

Centromeric localization and adaptive evolution of an Arabidopsis histone H3 variant.

Centromeric H3-like histones, which replace histone H3 in the centromeric chromatin of animals and fungi, have not been reported in plants. We identified a histone H3 variant from Arabidopsis thaliana that encodes a centromere-identifying protein designated HTR12. By immunological detection, HTR12 localized at centromeres in both mitotic and meiotic cells. HTR12 signal revealed tissue- and stage-specific differences in centromere morphology, including a distended bead-like structure in interphase root tip cells. The anti-HTR12 antibody also detected spherical organelles in meiotic cells. Although the antibody does not label centromeres in the closely related species Arabidopsis arenosa, HTR12 signal was found on all centromeres in allopolyploids of these two species. Comparison of the HTR12 genes of A. thaliana and A. arenosa revealed striking adaptive evolution in the N-terminal tail of the protein, similar to the pattern seen in its counterpart in Drosophila. This finding suggests that the same evolutionary forces shape centromeric chromatin in both animals and plants.

Adaptation, Physiological↗
PubMed2005

Fibulin-1C and Fibulin-1D splice variants have distinct functions and assemble in a hemicentin-dependent manner.

Fibulins are a family of extracellular glycoproteins associated with basement membranes and elastic fibers in vertebrates. Conservation of the fibulin-1 gene throughout metazoan evolution includes fibulin-1C and fibulin-1D alternate splice variants, although little is known about variant specific functions that would justify this striking structural conservation. We have therefore investigated the structure, localization and loss-of-function phenotype specific to both fibulin-1 variants in C. elegans. We find that fibulin-1C has specific roles during pharynx, intestine, gonad and muscle morphogenesis, being required to regulate cell shape and adhesion, whereas fibulin-1D assembles in flexible polymers that connect the pharynx and body-wall-muscle basement membranes. The assembly of fibulin-1C and fibulin-1D in multiple locations is dependent upon the presence of hemicentin, a recently described extracellular member of the immunoglobulin superfamily. We suggest that the distinct developmental roles and hemicentin-dependent assembly for fibulin-1 splice variants demonstrated here may be relevant to fibulin-1 and possibly other fibulin family members in non-nematode species.

Abdominal Muscles↗
PubMed2006

Gastrulation in the sea anemone Nematostella vectensis occurs by invagination and immigration: an ultrastructural study.

The sea anemone Nematostella vectensis has recently been established as a new model system for the understanding of the evolution of developmental processes. In particular, the evolutionary origin of gastrulation and its molecular regulation are the subject of intense investigation. However, while molecular data are rapidly accumulating, no detailed morphological data exist describing the process of gastrulation. Here, we carried out an ultrastructural study of different stages of gastrulation in Nematostella using transmission electron microscope and scanning electron microscopy techniques. We show that presumptive endodermal cells undergo a change in cell shape, reminiscent of the bottle cells known from vertebrates and several invertebrates. Presumptive endodermal cells organize into a field, the pre-endodermal plate, which undergoes invagination. In parallel, the endodermal cells decrease their apical cell contacts but remain loosely attached to each other. Hence, during early gastrulation they display an incomplete epithelial-mesenchymal transition (EMT). At a late stage of gastrulation, the cells eventually detach and fill the interior of the blastocoel as mesenchymal cells. This shows that gastrulation in Nematostella occurs by a combination of invagination and late immigration involving EMT. The comparison with molecular expression studies suggests that cells expressing snailA undergo EMT and become endodermal, whereas forkhead/brachyury expressing cells at the ectodermal margin of the blastopore retain their epithelial integrity throughout gastrulation.

Animals↗
PubMed2005

An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.

The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.

Animals↗
PubMed1988

Proteasomes (multi-protease complexes) as 20 S ring-shaped particles in a variety of eukaryotic cells.

Latent multicatalytic protease complexes, named proteasomes, were purified to apparent homogeneity from various eukaryotic sources, such as human, rat, and chicken liver, Xenopus laevis ovary, and yeast (Saccharomyces cerevisiae), and their functional and structural properties were compared. They showed latency in breakdown of [methyl-3H]casein, but were greatly activated in various ways, such as by addition of polylysine. They all degraded three types of fluorogenic oligopeptides at the carboxyl side of basic, neutral, and acidic amino acids, and the three cleavage reactions showed different spectra for inhibition, suggesting that they had three distinct active sites. The proteasomes all seemed to be seryl endopeptidases with similar pH optima in the weakly alkaline region. Their physiochemical properties, such as their sedimentation coefficients (19 S to 22 S), diffusion coefficients (2.0-2.6 X 10(-7) cm2 s-1), molecular masses (700-900 kDa), and circular dichroic spectra, were similar. Their amino acid compositions were also very similar. Electron microscopy showed that they had similar well-defined symmetrical morphology, appearing to be ring-shaped particles with a small hole in the center. All the proteasomes seemed to be multisubunit complexes consisting of 15-20 polypeptides with molecular masses of 22-33 kDa and isoelectric points of pH 3-10, but they showed species-specific differences in subunit multiplicity. Moreover, they differed immunologically, as shown by Ouchterlony tests and immunoblotting analyses, although cross-immunoreactivities of some subunits or domains were observed. These results indicate that the sizes and shapes of these proteasomes have been highly conserved during evolution, but that they show species-specific differences in immunoreactivities and subunit structures. Thus proteasomes with similar structure and function seem to be ubiquitously distributed in eukaryotic organisms ranging from man to yeast. This distribution implies the general importance of these proteasomes for proteolysis.

Amino Acids↗
PubMedDate not supplied

Ultrastructural and immunohistochemical contribution to the histogenesis of human cardiac myxoma.

The ultrastructural features of 8 human cardiac myxomas were analyzed and correlated with immunohistochemical data, with the aim to clarify the characteristics of the cell lines involved in the tumor genesis. Immunohistochemical studies were performed to detect the presence and the distribution of intracytoplasmic filaments (vimentin, desmin, actin, myosin) as well as myoglobin and factor VIII-related antigen, albumin, and lysozyme. Eighty percent of myxoma cells were simultaneously positive for vimentin, desmin, and actin, whereas 30% of them stained with antifactor VIII and antivimentin antibodies. The submicroscopic analysis revealed two main cell populations: (1) one composed of stellate-shaped cells with scanty organelles and sparse hyaloplasmic filaments scattered throughout the myxoid stroma and forming a loose network with their projections; (2) another one included cells with more cytoplasmic organelles, intermediate filaments, and myofilaments arranged either singly or in both solid and hollow cord-like structures. Our results support the hypothesis that cardiac myxoma may originate from a reserve multipotent mesenchymal cell able to differentiate more or less completely along two major evolutional lines: myoid and endothelial. The tumor tissue thus seems to be involved in vessel formation, suggesting a growth pattern akin to that manifested in other forms of endocardial pathological reactivity in which reserve mesenchymal cells are engaged.

Adult↗
PubMed2006

Evolutionary basis of codon usage and nucleotide composition bias in vertebrate DNA viruses.

Understanding the extent and causes of biases in codon usage and nucleotide composition is essential to the study of viral evolution, particularly the interplay between viruses and host cells or immune responses. To understand the common features and differences among viruses we analyzed the genomic characteristics of a representative collection of all sequenced vertebrate-infecting DNA viruses. This revealed that patterns of codon usage bias are strongly correlated with overall genomic GC content, suggesting that genome-wide mutational pressure, rather than natural selection for specific coding triplets, is the main determinant of codon usage. Further, we observed a striking difference in CpG content between DNA viruses with large and small genomes. While the majority of large genome viruses show the expected frequency of CpG, most small genome viruses had CpG contents far below expected values. The exceptions to this generalization, the large gammaherpesviruses and iridoviruses and the small dependoviruses, have sufficiently different life-cycle characteristics that they may help reveal some of the factors shaping the evolution of CpG usage in viruses.

Animals↗